This proposal is for basic research on the adult stem cells from bone marrow stroma referred to as mesenchymal stem cells or marrow stromal cells (MSCs). The overall aims of the proposal are: (a) to improve our understanding of the basic biology of human MSCs (hMSCs); (b) to develop new protocols for the ex vivo expansion of hMSCs and (c) to develop ex vivo and in vivo assays for the cells that will be of value for both further basic research with the cells and for their potential clinical applications to diseases of lung. The Specific Aims are: (1) Elucidate the molecular events that permit and enhance ex vivo expansion of hMSCs. (2) Develop an ex vivo assay for the potential of hMSCs to repair injured lung by co-culturing hMSCs with lung cells that have been damaged by heat-shock and hypoxia. (3) Develop an in vivo assay for engraftment and differentiation of hMSCs to sites of tissue injury in lung. (4) Identify the properties of hMSCs that enhance their engraftment to specific sites of tissue injury in lung.